A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: This study primarily aimed to evaluate the efficacy and safety of SaiLuoTong (SLT) on cognition in mild cognitive impairment (MCI). METHODS: Community-dwelling people with MCI aged ≥60 years were randomly assigned to 180 mg/day SLT or placebo for 12 weeks. RESULTS: Thirty-nine participants were randomized to each group (N = 78); 65 were included in the final analysis. After 12 weeks, the between-groups difference in Logical Memory delayed recall scores was 1.40 (95% confidence interval [CI]: 0.22 to 2.58; P = 0.010); Delis-Kaplan Executive Function System Trail Making Test Condition 4 switching and contrast scaled scores were 1.42 (95% CI: -0.15 to 2.99; P = 0.038) and 1.56 (95% CI: -0.09 to 3.20; P = 0.032), respectively; Rey Auditory Verbal Learning Test delayed recall was 1.37 (95% CI: -0.10 to 2.84; P = 0.034); and Functional Activities Questionnaire was 1.21 (95% CI: -0.21 to 2.63; P = 0.047; P < 0.001 after controlling for baseline scores). DISCUSSION: SLT is well tolerated and may be useful in supporting aspects of memory retrieval and executive function in people with MCI. Highlights: SaiLuoTong (SLT) improves delayed memory retrieval and executive function in people with mild cognitive impairment (MCI).SLT is well tolerated in people ≥ 60 years.The sample of community dwellers with MCI was well characterized and homogeneous.

The Effects of Cannabinoids on Pro- and Anti-Inflammatory Cytokines: A Systematic Review of In Vivo Studies.

Introduction: Some cannabinoids have been identified as anti-inflammatory agents; however, their potential therapeutic or prophylactic applications remain controversial. The aim of this systematic review was to provide a timely and comprehensive insight into cannabinoid-mediated pro- and anti-inflammatory cytokine responses in preclinical in vivo studies. Methods and Materials: A systematic search was conducted using PubMed, Web of Science, EMBASE, and Scopus. Eligible studies where cannabinoids had been evaluated for their effect on inflammation in animal models were included in the analysis. Data were extracted from 26 of 4247 eligible full text articles, and risk of bias was assessed using the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Studies examined cannabidiol (CBD; n=20); cannabigerol (CBG; n=1); delta 9-tetrahydrocannabinol (THC; n=2); THC and CBD separately (n=1); and THC and CBD in combination (n=2). Results: Tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, and interferon gamma were the most commonly studied pro-inflammatory cytokines and their levels were consistently reduced after treatment with CBD, CBG, or CBD+THC, but not with THC alone. The association between cannabinoid-induced anti-inflammatory response and disease severity was examined. In 22 studies where CBD, CBG, or CBD in combination with THC were administered, a reduction in the levels of at least one inflammatory cytokine was observed, and in 24 studies, some improvements in disease or disability were apparent. THC alone did not reduce pro-inflammatory cytokine levels (n=3), but resulted in improvements in neuropathic pain in one study. Conclusions: This review shows that CBD, CBG, and CBD+THC combination exert a predominantly anti-inflammatory effect in vivo, whereas THC alone does not reduce pro-inflammatory or increase anti-inflammatory cytokines. It is anticipated that this information could be used to inform human clinical trials of cannabinoids, focusing on CBD and CBG to reduce inflammation across a range of pathophysiological processes.

The Efficacy of Ketogenic Therapies in the Clinical Management of People with Neurodegenerative Disease: A Systematic Review.

Ketone bodies have potential disease-modifying activity that represent a novel therapeutic approach for neurodegenerative diseases (NDD). The aim of this systematic review was to summarize and evaluate the evidence for the application of ketogenic therapies (dietary or exogenous ketogenic agents) for NDD and provide recommendations for future research. Eight databases were electronically searched for articles reporting on controlled trials (≥4 wk duration) that induced ketosis or elevated serum ketone concentrations in people with NDD. Of 4498 records identified, 17 articles met the inclusion criteria with a total of 979 participants including studies on mild cognitive impairment (MCI; n = 6), multiple sclerosis (n = 4), Alzheimer's disease (n = 5), Parkinson's disease (n = 1), and MCI secondary to Parkinson's disease (n = 1). Of 17 studies, 7 were randomized double-blind placebo-controlled trials. Most studies used dietary interventions (n = 9), followed by medium-chain triglycerides (n = 7) and a fasting protocol (n = 1). Generally, trials were 6 wk in duration and assessed cognition as the primary outcome. Studies were heterogeneous in type and severity of NDD, interventions used, and outcomes assessed. Overall, 3/17 studies carried a low risk of bias. Based on available evidence, exogenous ketogenic agents may be more feasible than dietary interventions in NDD from a compliance and adherence perspective; more research is required to confirm this. Recommendations for future research include improving exogenous formulations to reduce adverse effects, exploring interindividual factors affecting response-to-treatment, and establishing a "minimum required dose" for clinically meaningful improvements in disease-specific symptoms, such as cognition or motor function.